Gyrase inhibitors are antibiotics which block the enzyme DNA gyrase which is a member of the topoisomerase 2 family. These enzymes fold the DNA helix on the surface of RNA cores to form loops and the loops are at the same time additionally twisted into a spiral. This results in an arrangement which requires a minimum amount of space. At the same time rapid replication, transcription and recombination of the DNA is promoted by this arrangement. If the function of this enzyme is inhibited or completely blocked by an active substance, a central, vitally important site of the dividing cell is affected and it is no longer viable.
Previously various fluorine-containing gyrase inhibitors have been used in their low-molecular form such as e.g. norfloxacin, enoxacin or ciprofloxacin to treat bacterial inflammations. A disadvantage of previous treatments using gyrase inhibitors is in particular the short retention time of the substances in the circulation so that they only have a very narrow time window to develop their activity. This is a fundamental problem of drug treating a disease with gyrase inhibitors which is based on a rapid renal and hepatobiliary elimination. Thus, for example after an oral dose of 400 mg norfloxacin a maximum of 1 μg/ml blood would be expected within a period of one hour which corresponds to an available amount of 1 to 2% of the administered total dose. Another disadvantage of the previously used gyrase inhibitors is that only a small proportion of the administered drug reaches the target site. This results in undesired side-effects which are mainly due to the fact that by far the largest proportion of the active substances is taken up by healthy organs where they cause side-effects. Observed side-effects are for example complaints in the area of the gastrointestinal tract, of the circulation and of the peripheral and central nervous system such as heightened excitability, restlessness, sleep disorders, disorientation and even to the extent of hallucinations and cramps as well as drowsiness extending to psychotic conditions. In addition skin disorders especially due to photo-sensitization as well as disorders of blood cell formation such as for example thrombocytopenia, leucopenia etc. have been observed.
P. Hammer and W. Heeschen (“Milchwissenschaft” 1995, 50(9), p. 513-514) disclose a method for producing an enrofloxacin-bovine serum albumin conjugate using N-hydroxysuccinimide, anhydrous dimethylformamide and dicyclohexyl-carbodiimide (DCC). The conjugate is used as an immunogen to produce antibodies and the antibody which is specific for enrofloxacin and ciprofloxacin is used in an indirect competitive immunoassay (ELISA). A major disadvantage of the conjugate disclosed by Hammer and Heeschen et al. is, however, the stated high molar ratio of enrofloxacin to bovine serum albumin which is about 25:1 because with such a high loading one can on no account assume that the protein is in its natural form but rather that the protein is massively denatured. However, this denaturation was the aim of Hammer and Heeschen because the immunization to obtain antibodies can only be successfully carried out with such a denatured protein. Thus, a denatured product that can no longer be administered is present which does not come into consideration for clinical use. It can no longer be ensured that the active substance is released directly at the site of action and is thus free of side-effects. Hence, the conjugate disclosed by Hammer and Heeschen is used exclusively in vitro to detect the gyrase inhibitors enrofloxacin and ciprofloxacin in the raw milk of cows.